pH-Responsive Coacervate Droplets Formed from Acid-Labile Methylated Polyrotaxanes as an Injectable Protein Carrier
pH-Responsive Coacervate Droplets Formed from Acid-Labile Methylated Polyrotaxanes as an Injectable Protein Carrier
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DOI：
10.1021/acs.biomac.8b00301
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发表时间：
2018-06-01
影响因子：
6.2
通讯作者：
Yui, Nobuhiko
中科院分区：
文献类型：
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作者：
Nishida, Kei;Tamura, Atsushi;Yui, Nobuhiko
在先前的研究中，已经证明甲基化β-环糊精-螺纹酸不稳定聚轮烷（Me-PRXs）表现出较低的临界溶解温度（LCST），并在高于其LCST时形成凝聚液滴。在这项研究中，蛋白质的凝聚液滴和pH响应释放的蛋白质的封装，通过酸诱导的Me-PRX的解离，进行了研究。凝聚液滴在pH 7.4下将各种蛋白质，如牛血清白蛋白（BSA）、溶菌酶和β-半乳糖苷酶包封到其疏水内相中。伴随着Me-PRXs的pH依赖性解离，凝聚物在pH 6.5以下降解并释放包封的蛋白质，保持蛋白质的固有活性。此外，在小鼠中皮下注射包封BSA的凝聚液滴显示，与游离BSA相比，BSA在注射部位的保留时间延长。总而言之，Me-PRX的凝聚液滴将被用作一类新的pH响应性和可注射载体，用于治疗性蛋白质的控制释放。
In prior research it has been demonstrated that methylated beta-cyclodextrins-threaded acid-labile polyrotaxanes (Me-PRXs) exhibit a lower critical solution temperature (LCST) and form coacervate droplets above their LCST. In this study, the encapsulation of proteins in coacervate droplets and the pH-responsive release of proteins, through the acid-induced dissociation of the Me-PRX, were investigated. The coacervate droplets encapsulate various proteins, such as bovine serum albumin (BSA), lysozyme, and beta-galactosidase, at pH 7.4, into their hydrophobic inner phase. Concomitant with the pH dependent dissociation of the Me-PRXs, the coacervates degraded below pH 6.5 and released encapsulated proteins, with the intrinsic activity of proteins maintained. Additionally, the subcutaneous injection of coacervate droplets encapsulating BSA in mice revealed that the retention time of the BSA at the injection site was prolonged compared to that of free BSA. Altogether, the coacervate droplets of the Me-PRX would be utilized as a new class of pH-responsive and injectable carrier for the controlled release of therapeutic proteins.